regulation of coronary blood flow · 2015. 2. 4. · regulation of coronary blood flow...

Regulation of Coronary Blood Flow

24-04-2104

Dirk J. Duncker

ETP April 24-26, 2014


• Introduction

• Control of Coronary Resistance Vessels

• Autoregulation: Pressure Flow Relation

• Hemodynamic Effects of a Coronary Stenosis

Duncker & Bache Physiol Rev 2008 Van de Hoeff et al J Mol Cell Cardiol 2012 Laughlin, …., Duncker Compr Physiol 2012 Canty & Duncker Braunwald’s Heart Disease 2014 ETP April 24-26, 2014

Cyclic Compression of the Coronary Microvasculature

Courtesy of Harold Laughlin

Duncker & Merkus 2004

GCV flow (ml/min)

0

80

160

RCA flow (ml/min)

0

10

20

LAD flow (ml/min)

0

60

120

Pressure (mmHg)

0

40

80

120 Ao

LV

RV

Time (s)

0.0 0.4 0.8 1.2

Systole Diastole Systole

ETP April 24-26, 2014

Unique aspects of the coronary circulation

• Cyclic compression of the vasculature

• High resting myocardial metabolic rate

Cardiac muscle 1 ml/min/g flow

Skeletal muscle 0.1 ml/min/g flow

High capillary density

Cardiac muscle 3000-4000/mm2

Skeletal muscle 500-1000/mm2

High oxygen extraction Cardiac muscle 60-80%

Skeletal muscle 20-30%

Myocardial O2 balance during exercise

(%)

(%)

(%)

(ml/m

in/g

)

MVO2 (ml/min/g)

0.0 0.2 0.4 0.6

0.0

0.5

1.0

1.5

2.0

2.5

3.0

90

100

MVO2 (ml/min/g)

0.0 0.2 0.4 0.6

0

10

20

30

40

50

CBF Hct

CVSO2

ArtSO2

*

*

** * *

*

* * * *

Von Restorff et al Pfluegers Arch 1977 ETP April 24-26, 2014

Myocardial O2 consumption (ml/min/g)

Coronary Flow Hematocrit

Coronary flow

[O2]ART - [O2]CV

80%

20%

LV work

Contractility

Heart Rate 60%

20%

20%

Basal metabolism

Contraction 100%

~0%

O2 supply

O2 demand

Myocardial O2 balance

Myocardial O2 balance during exercise

60%

80%

Duncker & Bache Physiol Reviews 2008 Duncker & Bache Physiol Reviews 2008 ETP April 24-26, 2014

Laughlin, Davis,…., Bache, Merkus, Duncker Compr Physiol 2012

Metabolic Vasodilation Exercise

LVMBF = LV Myocardial Blood Flow

ETP April 24-26, 2014

• Darcy’s law

ΔP = Flow x R

Flow =

• Poiseuille’s law

R =

Laws of Hemodynamics

r4 L

r h L = length r = radius h = viscosity R = resistance

Flow

P1 P2

P = pressure

R = resistance

R

8 h L

ΔP R

ΔP

JR Levick An Introduction to Cardiovascular Physiology 2010 ETP April 24-26, 2014


• Introduction





Chilian et al Am J Physiol 1989

Distribution of Resistance in Coronary Microcirculation

μ

Davis et al APS Handbook of Physiology 2008 Zhang, …, Chilian APS Handbook of Physiology 2008

μ

Control of tissue blood flow

“Blood goes where it is needed” John Hunter 1794

“He must have wondered how blood “knows” where it is needed?” LB Rowell JAP 2004

ETP April 24-26, 2014

The ultimate cardiac challenge Exercise

L S 1 2 3 Exercise (km/h)

4 5

CBF(ml/min)

LV dP/dt

(mmHg/s)

-2500

0

2500

5000

LVP(mmHg)

0

50

100

0

MAP(mmHg)

50

100

100

150

50

Rest Exercise at 5 km/h

Duncker et al. Circ Res 1998 Duncker & Merkus J Physiol 2007 Duncker & Bache Physiol Rev 2008 Laughlin, …, Duncker Compr Physiol 2012 ETP April 24-26, 2014

Neurohumoral influences Extravascular influences

NE

ACh

compression

Endothelial influences

histamine

bradykinin

ANG II

Endo- en Paracrine influences

PO2

adenosine

Metabolic influences

ANG I ANG II

bET-1 ET-1

ETA ETB

L-Arg NO PGI2

cAMPcGMP

Endothelium

Smooth Muscle

Cardiomyocyte

ADP

P2Y

shear stress

AA

adenosine

A2

O2• -

O2

O2

CO2

EDHF

ATP

KCa

AT1

ß2

H2O2

KCa

α1

α2

Erythrocytes

O2

NO

ATP

NE

H1

P2XH1

ETB

B2M

H2

M

AChNEKV

TXA2 5HT

TXA25HT

ACE

Platelets

TXA2 5HT

KATPKCa

KATP

ECE eNOS COX-1 CYP450

PCO2, H+, K+

IP

α2

Control of Coronary Microvascular Tone

Duncker & Bache Physiol Reviews 2008 ETP April 24-26, 2014

Neurohumoral influences Extravascular influences

NE

ACh

compression

Endothelial influences

histamine

bradykinin

ANG II

Endo- en Paracrine influences

PO2

adenosine

Metabolic influences

ANG I ANG II

bET-1 ET-1

ETA ETB

L-Arg NO PGI2

cAMPcGMP

Endothelium

Smooth Muscle

Cardiomyocyte

ADP

P2Y

shear stress

AA

adenosine

A2

O2• -

O2

O2

CO2

EDHF

ATP

KCa

AT1

ß2

H2O2

KCa

α1

α2

Erythrocytes

O2

NO

ATP

NE

H1

P2XH1

ETB

B2M

H2

M

AChNEKV

TXA2 5HT

TXA25HT

ACE

Platelets

TXA2 5HT

KATPKCa

KATP

ECE eNOS COX-1 CYP450

PCO2, H+, K+

IP

α2

Duncker & Bache Physiol Reviews 2008

Control of Coronary Microvascular Tone

ETP April 24-26, 2014


• Introduction





Autoregulation

The ability of the heart to maintain flow constant in the face of a change in perfusion pressure

without the intervention of any other external mechanism

ww

w.c

ard

io-a

als

t.b

e

ETP April 24-26, 2014 (Courtesy of Bernard De Bruyne)

25

50

75

100

125

150

175

200

0 25 50 75 100 125 150 175 200

Coronary Perfusion Pressure (mm Hg)

Co

ron

ary

Blo

od

Flo

w (

mL/

min

)

Rubio and Berne, Prog CV Disease 1975

Coronary Autoregulation


ww

w.c

ard

io-a

als

t.b

e

25

50

75

100

125

150

175

200

0 25 50 75 100 125 150 175 200

Coronary Perfusion Pressure (mm Hg)

Co

ron

ary

Blo

od

Flo

w (

mL/

min

)

Rubio and Berne, Prog CV Disease 1975

Autoregulatory Range

ww

w.c

ard

io-a

als

t.b

e


Zhang, Rogers, Merkus, … Chilian APS Handbook of Physiology 2008

Davis et al APS Handbook of Physiology 2008

μ

μ

Coronary Pressure-Flow Relation

Canty & Duncker Braunwald’s Heart Disease 2014 ETP April 24-26, 2014

ΔP = Flow x R

Rmin = ΔP/Flowmax

Cmax = 1/Rmin = Flowmax/ΔP

P = pressure

R = resistance

C = conductance

Coronary Pressure-Flow Relation Subendocardial Vulnerability


20

Coronary Flow-Function Relation Subendocardial vulnerability

ETP April 24-26, 2014 Canty Circ Res 1988; Canty et al Circulation 1990


• Introduction


• Autoregulation: Pressure Flow Relations



Stenosis

PAORTA

PDISTAL

ETP April 24-26, 2014

Coronary velocity

Pressure Derived Fractional Flow Reserve, FFR

Coronary (Pd)

Aortic (Pao)

Adenosine

CFR= 2.2

FFR= Pd/Pao = 105/133 = 0.78

ETP April 24-26, 2014

Canty & Duncker Braunwald’s Heart Disease 2014

Assessment of Coronary Reserve

Flow velocity wire

Pressure wire

PET/MRI/CT Perfusion


• Introduction


• Autoregulation: Pressure Flow Relations



Coronary Pressure-Flow Relation Influence of Coronary Microvascular Disease

ETP April 24-26, 2014 Canty & Duncker Braunwald’s Heart Disease 2014

regulation of coronary blood flow · 2015. 2. 4. · regulation of coronary blood flow...

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